Oral composition

ABSTRACT

An oral composition comprising cetylpyridinium chloride and a N.sup.α -longer acyl basic amino acid lower alkyl ester or a salt thereof. The oral composition of the present invention promotes adsorption of cetylpyridinium chloride as a bactericide to the surfaces of teeth and shows excellent prevention of formation of dental plaque and dental caries.

FIELD OF THE INVENTION

The present invention relates to a composition for the oral cavity. Moreparticularly, it relates to an oral composition wherein adsorption ofcetylpyridinium chloride as a bactericide to the surfaces of teeth ispromoted.

BACKGROUND OF THE INVENTION

Dental plaque is formed by adsorption and propagation of intraoralbacteria such as Streptococcus mutans and the like on the surfaces ofteeth. It is well known that dental plaque is the cause of dental cariesand is also the cause of gingivitis or alveolar pyorrhea. Therefore, itis important to remove dental plaque and to prevent adhesion of it(plaque control) for oral sanitation.

Among the plaque control methods, the method which is performed mostcommonly is that for removing dental plaque mechanically by brushing,that is, by using a toothbrush. However, in order to remove dentalplaque completely by brushing, high-level brushing technique is needed.In practice, almost all people are conducting insufficient brushing and,therefore, the rate of diseases such as dental caries, gingivitis andalveolar pyorrhea is not reduced despite brushing.

Accordingly, in order to compensate brushing, or to substitute forbrushing, a chemical plaque control method has been studied. Thepyridinium compounds having C₈₋₁₈ straight or blanched chain alkyl groupare known. Among them, the compound of which efficacy and safety areclinically acknowledged is cetylpyridinium chloride.

It is known that cetylpyridinium chloride is a compound represented bythe formula: ##STR1## and it has a bactericidal action and is easily toadsorbed to oral mucosa or the surfaces of teeth. Thereby, it isconsidered that adsorption of intraoral bacteria to the surfaces ofteeth is prevented and, further, formation of dental plaque isprevented. However, a study on promoting adsorption of suchcetylpyridinium chloride to the surfaces of teeth or on improving it'seffect has not been performed yet.

The present inventors have intensively studied to promote retention ofcetylpyridinium chloride in the oral cavity, particularly adsorption ofit to the surfaces of teeth and to enhance the effect of preventingformation of bacterial plaque. As a result, it has been found that, whencetylpyridinium chloride is used in combination with an N.sup.α -longeracyl basic amino acid lower alkyl ester or a salt thereof, adsorption ofcetylpyridinium chloride to the surfaces of teeth is greatly enhanced.Thus, the present invention has been completed.

DISCLOSURE OF THE INVENTION

According to the present invention, there is provided an oralcomposition comprising cetylpyridinium chloride and an N.sup.α -longeracyl basic amino acid lower alkyl ester or a salt thereof. According tothe present invention, an oral composition which promotes adsorption ofcetylpyridinium chloride to the surfaces of teeth and has excellenteffect for preventing formation of dental plaque and dental caries canbe obtained.

Cetylpyridinium chloride is normally formulated into the composition inan amount of more than 0.002 % by weight, preferably more than 0.01 % byweight. In view of bactericidal effect, the upper limit of the amount ofcetylpyridinium chloride is not specifically limited. Considering thefact that cetylpyridinium chloride has a bitter taste and is likely tocolor teeth when the amount is too large, or influence on oral mucosaand the like, it is normally preferred that the amount is less than 1 %by weight.

As the basic amino acid part of the N.sup.α -longer acyl basic aminoacid lower alkyl ester to be used, ornithine, lysine and arginine areparticularly preferred and it may be either an optical isomer orracemate thereof. The acyl group thereof is a saturated or unsaturatednatural or synthetic fatty acid residue having 8 to 22 carbon atoms, forexample, it may be a natural system mixed fatty acid residue such ascoconut oil fatty acid, tallow fatty acid residue and the like, inaddition to a monofatty acid residue such as lauroyl, myristyl, stearoylgroup and the like. Further, it may also be a lower alkyl ester, such asmethyl ester, ethyl ester and propyl ester are.

Examples of the salt of the N.sup.α -longer basic amino acid lower alkylester include an inorganic acid salt such as hydrochloride, sulfate,etc. or an organic acid salt such as acetate, tartrate, citrate,p-toluenesulfonate, fatty acid salt, acidic amino acid salt, etc. Amongthem, glutamate, pyroglutamate, acetate and citrate are preferred.

In the present invention, the N.sup.α -longer basic amino acid loweralkyl ester or a salt thereof is that which promotes adsorption ofcetylpyridinium chloride to the surfaces of teeth. The weight ratiothereof is at least 1/5, normally 1/5 to 10 based on the weight ofcetylpyridinium chloride. When the ratio is too small, the effect ofpromoting adsorption of cetylpyridinium chloride to teeth becomesinsufficient.

The oral composition of the present invention can be prepared in theform of tooth powder, dentifrice, mouthwash, troches and the like byformulating desired ingredients according to a conventional method and,further, it can be sprayed in the oral cavity as an aerosol. Further, itcan be used for a liniment and also used after being impregnated in adental floss or toothpick.

The other ingredients formulated may be any ingredients which can beused in this kind of compositions in so far as they do not inhibitadsorption of cetylpyridinium chloride to the surfaces of teeth and itsbactericidal action. In the case of using vesicants or solubilizers,anionic ingredients are not preferred. It has been found that, whenusing nonionic or cationic ingredients, particularly, polyoxyethylenepolyoxypropylene glycol, ethylenediaminetetrapolyoxyethylenepolyoxypropylene glycol and the like, the effect of cetylpyridiniumchloride is further improved.

EXAMPLES

The following Experiments and Examples further illustrate the presentinvention in detail but are not to be construed to limit the scopethereof. In Experiments and Examples, all percentages are by weightunless otherwise stated.

Experiment 1

Adsorption test of cetylpyridinium chloride to the

surfaces of teeth

The composition of enamel of the surfaces of teeth consists of inorganicmineral (97 %), organic material (1%) and water content (2 %), and amain ingredient of the mineral is calcium phosphate which is referred toas hydroxyapatite [Ca₁₀ (PO₄)₆ (OH)₂ ].

As a model of enamel of teeth, that obtained by dipping a hydroxyapatitedisc [Bio-Gel HTP manufactured by Bio. Rad. Laboratories Co., U.S.A., 13mmφ ×250 mg; prepared by making tablets at 150 kg/cm² and sintering at600° C. for 6 hours] in human saliva at 37° C. for 18 hours was used. Bydipping in saliva, saliva mucoprotein, etc. was adsorbed to the surfaceof hydroxyapatite to be allowed to simulate an actual state of toothenamel wetted with saliva. This hydroxyapatite disc treated with salivawas placed in a test tube, followed by the addition of an aqueous 0.05 %cetylpyridinium chloride (manufactured by Merck Co.) solution (1 ml) andshaking at 37° C. for 30 minutes. Thereafter, it was washed with water(6 ml) and extracted with an extraction solvent [50 mM sodium laurylsulfate, 40 mM citrate buffer (pH 3.0)/acetonitrile =30/70] to form asample for high speed liquid chromatography. In the case of high speedliquid chromatography, Lichrosorb RP select B (4.0 mmφ ×250 mm) was usedas a separation column and a extraction solvent was used as an eluent.The flow rate was 1 ml/minutes and detection of cetylpyridinium wasconducted by measuring absorbance with 258 nm. Further, by using acalibration curve made by a standard solution of cetylpyridiniumchloride, the amount of cetylpyridinium chloride was determined.

Likewise, after an apatite disc treated with saliva was dipped in amixed solution in which various additives as shown in Table 1 were addedto 0.05 % cetylpyridinium chloride in an amount of 0.1 %, respectively,the amount of cetylpyridinium chloride was determined. Further,regarding N.sup.α -cocoyl-L-arginine ethyl ester pyrrolidone carboxylateamong the additives which showed the effect for enhancing the amount ofcetylpyridinium chloride adsorbed on the apatite disc, by varying inamount between 0.005, 0.01 and 0.05 %, respectively, the influence ofthe concentration on the amount of cetylpyridinium chloride adsorbed wasconfirmed. The results are also shown in Table 1.

                  TABLE 1                                                         ______________________________________                                                          Amount of cetylpyridinium                                                     chloride (μg/disc)                                       Compound            Initial  After 3 hours                                    ______________________________________                                        0.05% Cetylpyridinium chloride                                                                    170       63                                              0.05% Cetylpyridinium chloride +                                                                  411      321                                              0.01% N.sup.α -cocoyl-L-arginine                                        methyl ester hydrochloride                                                    0.05% Cetylpyridinium chloride +                                                                  436      336                                              0.1% N.sup.α -lauroyl-L-arginine                                        methyl ester pyrrolidone                                                      carboxylate                                                                   0.05% Cetylpyridinium chloride +                                                                  438      346                                              0.1% N.sup.α -cocoyl-L-arginine ethyl                                   ester pyrrolidone carboxylate                                                 0.05% Cetylpyridinium chloride +                                                                  424      330                                              0.1% N.sup.α -palmitol-L-lysine                                         methyl ester acetate                                                          0.05% Cetylpyridinium chloride +                                                                   59       18                                              0.1% sodium N.sup.α -lauroyl methyl                                     taurine                                                                       0.05% Cetylpyridinium chloride +                                                                  173       60                                              0.1% sodium N.sup.α -lauroyl-methyl-b-                                  alanine                                                                       0.05% Cetylpyridinium chloride +                                                                  175      119                                              0.005% N.sup.α -cocoyl-L-arginine                                       ester pyrrolidone carboxylate                                                 0.05% Cetylpyridinium chloride +                                                                  331      242                                              0.01% N.sup.α -cocoyl-L-arginine                                        ethyl ester pyrrolidone                                                       carboxylate                                                                   0.05% Cetylpyridinium chloride +                                                                  392      294                                              0.05% N.sup.α -cocoyl-L-arginine                                        ethyl ester pyrrolidone                                                       carboxylate                                                                   ______________________________________                                    

As is shown in Table 1, when a N.sup.α -longer acyl basic amino acidlower alkyl ester is formulated, cetylpyridinium chloride isspecifically adsorbed to the hydroxyapatite disc and it is necessarythat the weight ratio is more than 1/5 based on the weight ofcetylpyridinium chloride.

EXPERIMENT 2

Since cetylpyridinium chloride is sometimes inactivated in the case offorming a salt with an acidic substance, retention of bactericidalactivity was also tested as follows.

Regarding a sample wherein adsorption of cetylpyridinium chloride to thehydroxyapatite disc was enhanced by adding the N.sup.α -longer acylbasic amino acid lower alkyl ester, a disc was suspended to a 5 %sucrose BHI medium. Then, one loopful of the Streptococcus mutans ATCC25175 strain was inoculated and cultivated at 37° C. for 18 hours. As aresult, adhesion of plaque to the hydroxyapatite disc was not observedand it was confirmed that cetylpyridinium chloride adsorbed on thehydroxyapatite disc retains bactericidal activity.

EXAMPLE 1

According to the following formulation, a toothpaste was prepared bydegassing, kneading and stirring according to a conventional method.

    ______________________________________                                        Ingredients          % by weight                                              ______________________________________                                        Calcium hydrogenphosphate                                                                          20.0                                                     Polyoxyethylene polyoxypropylene                                                                   30.0                                                     glycol                                                                        Glycerin             10.0                                                     Cetylpyridinium chloride                                                                            0.1                                                     N.sup.α -lauroyl-L-arginine methyl ester                                                      0.05                                                    pyrrolidone carboxylate                                                       Saccharin sodium      0.2                                                     Flavor                1.0                                                     Distilled water      up to 100%                                               ______________________________________                                    

EXAMPLE 2

According to the following formulation, a toothpaste was prepared bydegassing, kneading and stirring according to a conventional method.

    ______________________________________                                        Ingredients          % by weight                                              ______________________________________                                        Calcium carbonate    35.0                                                     Hydroxyethylcellulose                                                                              1.5                                                      Ethylenediamine tetrapolyoxy-                                                                      5.0                                                      ethylene polyoxypropylene glycol                                              Sorbitol             30.0                                                     Cetylpyridinium chloride                                                                            0.01                                                    N.sup.α -cocoyl-L-arginine methyl                                                             0.01                                                    ester hydrochloride                                                           Saccharin sodium     0.1                                                      Flavor               1.0                                                      Distilled water      up to 100%                                               ______________________________________                                    

EXAMPLE 3

According to the following formulation, a liquid mouthwash was preparedby mixing with stirring according to a conventional method.

    ______________________________________                                        Ingredients          % by weight                                              ______________________________________                                        Ethanol              10.0                                                     Glycerin             10.0                                                     Polyoxyethylene polyoxypropylene                                                                   1.5                                                      glycol                                                                        Saccharin sodium      0.02                                                    Cetylpyridinium chloride                                                                            0.05                                                    N.sup.α -cocoyl-L-arginine ethyl                                                             0.1                                                      ester pyrrolidone carboxylate                                                 Flavor               0.3                                                      Distilled water      up to 100%                                               ______________________________________                                    

EXAMPLE 4

A yarn of 630 deniers comprising a plurality of fine denier filaments of6,6-nylon being twisted was dipped in the mixed solution of thefollowing formulation, passed through a drying tube at 50° C. andspooled with vaporizing ethanol to produce a dental floss.

    ______________________________________                                        Ingredients          % by weight                                              ______________________________________                                        Cetylpyridinium chloride                                                                            5.0                                                     N.sup.α cocoyl-L-arginine ethyl ester                                                        10.0                                                     pyrrolidone carboxylate                                                       Ethanol              85.0                                                     ______________________________________                                    

What is claimed is:
 1. An oral composition consisting essentially of abactericidal effective amount of cetylpyridinium chloride and a N.sup.α-longer acyl basic amino acid lower alkyl ester or a salt thereof in anamount effective to promote the adsorption of cetylpyridinium chlorideto the surfaces of teeth, wherein the amount of cetylpyridinium chlorideis from 0.002% to 1% by weight of the composition.
 2. An oralcomposition according to claim 1, wherein the weight ratio of theN.sup.α -longer acyl basic amino acid lower alkyl ester tocetylpyridinium chloride is from 1/5 to
 10. 3. An oral compositionaccording to claim 2, wherein the N.sup.α -longer acyl basic amino acidlower alkyl ester is selected from the group consisting of N.sup.α-cocoyl-L-arginine methyl ester hydrochloride, N.sup.α-lauroyl-L-arginine methyl ester pyrrolidone carboxylate, N.sup.α-cocoyl -L-arginine ethyl ester pyrrolidone carboxylate, and N.sup.α-palmitoyl-L-lysine-methyl ester acetate.